Gender, Age, and Comorbidity Status Predict Improved Survival with Adjuvant Chemotherapy Following Lobectomy for Non-small Cell Lung Cancers Larger than 4 cm.

PURPOSE: To identify pretreatment prognostic factors associated with improved outcomes in patients with non-small cell lung cancer (NSCLC) tumors larger than 4 cm receiving adjuvant chemotherapy following surgery versus surgery alone. METHODS: Information was collected from the National Cancer Data Base on adults diagnosed with NSCLC who underwent lobectomy with or without adjuvant chemotherapy for pathologic T2 tumors measuring at least 4 cm, with no lymph node involvement or distant metastasis. The data were analyzed using model-based recursive partitioning for survival. RESULTS: Patients who underwent chemotherapy following surgery experienced a survival benefit compared with patients who were treated with surgery alone (5-year survival of 66 vs. 49 %, p<0.0001). Overall, women had improved 5-year survival relative to men (60 vs. 47 %, p<0.0001). Despite this observation, three groups of women experienced no benefit from adjuvant chemotherapy:women 65-72 years with a Charlson-Deyo (CD) score ≥1 (5-year survival: 51 vs. 58 %, p = 0.29), women >72 with a CD score = 0 (5-year survival: 53 vs. 56 %, p = 0.57), and women >72 with a CD score ≥1 (5-year survival: 40 vs. 56 %, p = 0.04). By contrast, all groups of men identified by recursive partitioning analysis demonstrated improved survivals with adjuvant chemotherapy. CONCLUSIONS: Adjuvant chemotherapy appears to increase survival for patients with resected NSCLC tumors larger than 4 cm. Women with NSCLC experience improved survival relative to men regardless of treatment. However,there are certain groups of women over 65 years old who do not benefit from adjuvant chemotherapy.

Evaluating the fate of patients who undergo resections of very large, node-negative lung cancers using the National Cancer DataBase.

OBJECTIVES: To determine whether there are differences in survival associated with different treatment modalities among patients with lymph node-negative, very large non-small-cell lung cancers (NSCLCs). METHODS: The National Cancer DataBase was used to identify patients diagnosed with NSCLCs >7 cm (T3) without lymph node involvement (N0) or metastatic disease (M0) from 1999 to 2006. Surgical therapy included surgery alone, neoadjuvant chemoradiation therapy or chemotherapy, surgery followed by adjuvant chemoradiation therapy or chemotherapy and surgery followed by postoperative radiation therapy (PORT). The 5-year overall survival (OS) was estimated by the Kaplan-Meier method and comparisons were made using log-rank tests and Cox regression models. RESULTS: Of the 2296 patients identified with cT3N0M0 disease, 45% underwent surgical therapy. The 5-year OS rate was 38%. Across the different treatment regimens, there was a significant difference in 5-year OS. Neither neoadjuvant chemoradiation therapy or chemotherapy nor adjuvant chemoradiation therapy was associated with improved 5-year OS. The use of adjuvant chemotherapy was associated with improved OS relative to surgery alone [hazard ratio (HR) 0.70; 95% confidence interval (CI) 0.54-0.91, P = 0.008]. PORT alone was associated with a detrimental effect on 5-year OS relative to surgery alone [HR 2.04; 95% CI 1.38-3.03, P < 0.001]. CONCLUSIONS: Large T3N0 NSCLCs appear to be optimally treated with surgical resection followed by adjuvant chemotherapy.

Now or later: evaluating the importance of chemotherapy timing in resectable stage III (N2) lung cancer in the National Cancer Database.

BACKGROUND: Preoperative chemotherapy improves the survival of surgically managed stage III non-small cell lung cancer (NSCLC). A proportion of stage III NSCLC patients in the United States have undergone operations primarily and been given chemotherapy postoperatively. It is unclear whether postoperative chemotherapy is as effective as preoperative chemotherapy. Our objective was to determine the survival of resected stage III NSCLC according to the timing of chemotherapy. METHODS: The National Cancer Database (NCDB) was queried for clinical T1-4N2M0 NSCLC (cstage III-cN2) undergoing lobectomy or pneumonectomy between 2003 and 2006. RESULTS: 1,356 patients with surgically managed cstage III-cN2 disease who received preoperative chemotherapy were compared with 649 patients receiving postoperative chemotherapy. In a Cox proportional hazards model with adjustment for demographics, comorbidities, and tumor attributes, the results of postoperative chemotherapy appeared similar to those of preoperative chemotherapy (hazard ratio [HR] = 1.05, 95% confidence interval [CI] 0.93-1.19, p = 0.438). In separate Cox models, the results of postoperative chemotherapy alone were similar to those of preoperative chemotherapy alone (HR = 1.106, 95% CI 0.91-1.344, p = 0.3124). The results of postoperative chemotherapy + radiation were similar to those of preoperative chemotherapy + radiation (HR = 1.125, 95% CI 0.949-1.333, p = -0.175). CONCLUSIONS: Adjusted comparison of preoperative and postoperative chemotherapy results for cstage III-N2 NSCLC in the NCDB failed to identify a superior chemotherapy approach. This suggests that a more rigorous examination of the widely held view that preoperative chemotherapy is superior may be warranted.

Impact of adjuvant treatment for microscopic residual disease after non-small cell lung cancer surgery.

BACKGROUND: Incomplete resection of non-small cell lung cancer (NSCLC) portends a dramatic decline in survival. Historically, postoperative radiation and chemotherapy have been offered to treat residual disease at the surgical margins, yet the efficacy is unknown. We examined the survival among incompletely resected NSCLC patients to identify the optimal response to positive NSCLC surgical margins. METHODS: The National Cancer Data Base was queried for surgically managed pathologic stage I-III NSCLC between 2003 and 2006 (n = 54,512). The prevalence, predictors, impact, and optimal treatment approaches to positive surgical margins were investigated. RESULTS: A positive surgical margin was identified in 3,102 NSCLC patients (5.7% of resections), including 1,688 with microscopically positive (R1) margins (3.1%). Compared with complete resections, patients with R1 resections had a worse 5-year survival; stage pI (62% vs 37%; p < 0.0001), stage pII (41% vs 29%; p < 0.0001), and stage pIII (33% vs 19%; p < 0.0001). Postoperative administration of both chemotherapy and radiation were associated with superior survival compared with surgery alone at all stages; stage pI (44% vs 35%; p = 0.05), stage pII (33% vs 21%; p = 0.0013), and stage pIII NSCLC (30% vs 12%; p < 0.0001). Administration of chemotherapy or radiation alone was less consistently associated with improved outcome in R1 patients. Of note, radiation alone did not improve survival for stage pI patients with R1 resections (26% vs 35%; p = 0.0399). CONCLUSIONS: The administration of both chemotherapy and radiation is associated with an improved survival in patients with microscopically positive surgical margins, irrespective of stage. Further study is needed to clarify the optimal stage-specific adjuvant approach to incompletely resected NSCLC.

Bolstering the case for lobectomy in stages I, II, and IIIA small-cell lung cancer using the National Cancer Data Base.

INTRODUCTION: Current therapy for small-cell lung cancer (SCLC) relies on chemoradiation therapy, and the role of primary surgical resection in these patients remains controversial. A minority of SCLC patients present without metastatic disease and are candidates for surgery. This study investigates the role of surgical resection in select patients with SCLC, using a national cohort of approximately 2500 resected patients. METHODS: A retrospective study of SCLC patients in the National Cancer Data Base (NCDB) was performed where patients were grouped for comparison by stage and treatment regimen. Survival was estimated by Kaplan-Meier methods and multivariate comparisons using Cox regression. RESULTS: Of 28,621 cases of potentially resectable SCLC, 2476 patients (9%) underwent surgery of the primary site with curative intent. Five-year overall survival for patients after resection was 51%, 25%, and 18% for clinical stages I, II, and IIIA, respectively. Addition of surgery to chemotherapy was associated with decreased likelihood of death (hazard ratio: 0.57, 95% confidence interval: 0.47-0.68), independent of age, stage, and comorbidity score. Lobectomy was associated with a 5-year overall survival of 40% compared with 21% and 22% for sublobar resection and pneumonectomy, respectively. Hazard ratio for death after sublobar resections compared with lobectomy was 1.38 (95% confidence interval: 1.12-1.71). CONCLUSIONS: Patients with stages I, II, and III SCLC, who underwent surgical resection as part of initial treatment with chemotherapy had respectable OS. These data may warrant prospective studies of including surgery in the multimodality treatment of SCLC in specific circumstances.

Predictors of mortality after surgical management of lung cancer in the National Cancer Database.

BACKGROUND: Surgical resection represents the standard of care for locoregionally confined non-small cell lung cancer (NSCLC); however, surgical complications may compromise the overall outcome. Adverse events after lung cancer surgery have been studied extensively, yet available databases have significant limitations (with respect to size, provider, patient age, and so forth). The National Cancer Database (NCDB) is the largest cancer registry in the world, capturing 67% of newly diagnosed NSCLC in the United States. We studied surgically managed NSCLC patients in the NCDB to more accurately assess factors that influence perioperative outcomes. METHODS: Patients diagnosed with NSCLC from 2004 to 2009 in the NCDB who were managed with surgical resection were included (n = 119,146). Primary endpoints included death within 30 days of surgery and extended length of stay (more than 14 days). RESULTS: Overall 30-day mortality rate was 3.4% and varied by procedure: lobectomy/bilobectomy (2.6%), wedge resection (4.2%), extended lobectomy/bilobectomy (4%), and pneumonectomy (8.5%). By multivariable analysis, increasing age, male sex, increasing comorbidities, and decreased facility volume were associated with higher 30-day mortality. Of patients who underwent lobectomy, 9.1% had an extended length of stay. On multivariable analysis, increasing age, male sex, increasing comorbidities, decreasing facility volume, and right-sided tumors were associated with increased incidence of extended length of stay. CONCLUSIONS: Adverse events after the surgical treatment of NSCLC in the NCDB occur with a similar frequency and are predicted by similar patient, procedural, and facility variables as have been identified by more restricted data resources. The NCDB appears to be a valuable resource to study NSCLC in the United States.